Chronic pain is a major contributor to disability in the industrialized world and is the cause of an untold amount of suffering. The successful treatment of severe and chronic pain is a primary goal of the physician, with opioid analgesics being the current drugs of choice.
Opioid analgesics (i.e., opioids'having analgesic properties) are drugs that function in a manner similar to that of morphine. These agents work by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. Although the term opiate is often used as a synonym for opioid, it is more frequently used to refer to the natural opium alkaloids and the semi-synthetics derived from them.
An important goal of analgesic therapy is to achieve continuous relief of chronic pain. Regular administration of an analgesic is generally required to ensure that the next dose is given before the effects of the previous dose have worn off. Compliance with opioids increases as the required dosing frequency decreases. Non-compliance results in suboptimal pain control and poor quality-of-life outcomes. Scheduled rather than “as needed” administration of opioids is currently recommended in guidelines for their use in treating chronic non-malignant pain. Unfortunately, evidence from prior clinical trials and clinical experience suggests that the short duration of action of immediate-release opioid formulations would necessitate 4-hourly administrations in order to maintain optimal levels of analgesia in patients with chronic pain. Moreover, immediate-release formulations can exhibit low oral bioavailability. Thus, there is a need for new opioid-containing oral pharmaceutical compositions that provide sustained release, and ideally zero-order release kinetics, and less frequent dosing.
Opioids (particularly those with analgesic activity) are sometimes the subject of abuse. Typically, a particular dose of an opioid analgesic is more potent when administered parenterally as compared to the same dose administered orally. Therefore, one popular mode of abuse of oral opioid formulations involves the extraction of the opioid from the dosage form, and the subsequent injection of the opioid (using any “suitable” vehicle for injection) in order to achieve a “high.” Also, some formulations can be tampered with in order to provide the opioid contained therein better availability for illicit use. For example, an opioid-containing tablet can be crushed in order to render the opioid therein available for immediate release upon oral, nasal, or intravenous administration. An opioid formulation can also be abused by administration of more than the prescribed dose of the drug. Thus, there is a need for new opioid-containing oral pharmaceutical compositions that provide abuse deterrence in addition to providing sustained-release, ideally zero-order release kinetics, and less frequent dosing.